The availability of effective treatment for hypercholesterolemia raises the hope that millions of Americans can avoid or postpone the development of heart disease. Because the interventions are potentially effective but may also be costly, the cost-effectiveness of alternative approaches to detecting and treating hypercholesterolemia has become a critical issue for health policy. The proposed investigation of the cost-effectiveness of alternative strategies for cholesterol reduction includes assessments of: 1) effects of treatment on health outcomes (symptomatic coronary heart disease, death from coronary heart disease, and mortality from all causes); 2) costs and effectiveness of specific dietary and pharmacological interventions; 3) effects of delays in instituting treatment; 4) effects of changing the interval between blood cholesterol tests on the probability and duration of treatment delay; 5) cost and health consequences of modifying screening and treatment recommendations for other risk factors, age, and gender; 6) population implications of screening and treatment strategies. The principal data source for the investigation is the Framingham Heart Study. Data from the study will be used to estimate the time pattern of cholesterol levels, which is fundamental to the evaluation of changing the interval between cholesterol tests. Framingham data will also be used to estimate the relation of event rates to blood cholesterol levels. Several components of the analysis will be validated by testing model predictions against data from the Multiple Risk Factor Intervention Trial. The cost estimates will be based on several additional sources. Individual-level cost-effectiveness estimates for several different interventions will be presented along with population-level projections of the consequences of alternative strategies. The significance of altering assumptions about uncertain values, such as the long-term risks and benefits of specific medications, will be tested in sensitivity analyses.